Y. B. Gordon

FETAL LOSS AFTER IMPLANTATION: A Prospective Study

The incidence of post-implantation pregnancy loss in 197 women was determined prospectively. The diagnosis of pregnancy was based on the detection of human chorionic gonadotropin in the urine during the luteal phase of each menstrual cycle. There were 152 conceptions in the 623 cycles studied with a pregnancy loss rate of 43%. 14 of the pregnancies ended in clinically recognised spontaneous abortions and in 50 the sole evidence of pregnancy was an increased concentration of urinary hCG. The maximum conception rate achieved was 36% in the first cycle after removal of an intra uterine device.

SPECIFIC AND SENSITIVE DETERMINATION OF PREGNANCY-SPECIFIC β1-GLYCOPROTEIN BY RADIOIMMUNOASSAY: A New Pregnancy Test

A specific and highly sensitive radioimmunoassay (R.I.A.) for determination of pregnancy-specific beta 1-glycoprotein (S.P.1) in human plasma, urine, amniotic fluid, and breast milk has been developed. The minimum detection limit of S.P.1 was 8 mug/1 of sample. The assay was applied to plasma and/or urine samples from 8 women in early pregnancy. S.P. 1 was detected in the plasma of all three women obtained within 14 days of ovulation, the earliest positive result being at 7 days. In another woman plasma was negative at day 18 and positive by day 22. In the three remaining women plasma S.P.1 was detected when measured within 24 to 36 days of ovulation. S.P.1 was detected in four urine samples obtained between 20 and 28 days after ovulation. S.P.1 was also measured in breast milk, amniotic fluid, cord blood, and plasma of women with ectopic gestation and trophoblastic disease. It is suggested that the assay of S.P.1 may have important advantages over existing systems for detection and monitoring of early pregnancy.

CONCENTRATIONS OF PREGNANCY-SPECIFIC β1-GLYCOPROTEIN IN MATERNAL BLOOD IN NORMAL PREGNANCY AND IN INTRAUTERINE GROWTH RETARDATION

A radioimmunoassay has been developed for pregnancy-specific beta 1-glycoprotein (S.P.1), a product of the human placenta. Circulating concentrations of S.P.1 were measured in 153 women in the third trimester of normal pregnancy and in 27 women who delivered children with birth-weight below the 10th centile of the normal range--i.e., with intrauterine growth regardation (I.U.G.R.). Concentrations of S.P.1 showed a skewed distribution and rose progressively to reach a plateau in the last four weeks of pregnancy. In over 70% of women with I.U.G.R. of the fetus, concentrations of S.P.1 were low. Measurement of serum-S.P.1 may provide a new index of fetal wellbeing.

LEVELS OF ALPHA-FETOPROTEIN IN MATERNAL BLOOD AS A SCREENING TEST FOR FETAL NEURAL-TUBE DEFECT

A range has been established for maternal plasma-alpha-fetoprotein (A.F.P.) levels in normal pregnancies (930 women). A.F.P. levels between 10 and 40 weeks gestation were examined in 51 pregnancies associated with fetal neural-tube defect. In 96% of cases (20 anencephalus, 6 spina bifida) examined between 16 and 26 weeks of gestation A.F.P. levels were above the 95th centile of the normal range. It is suggested that measurement of A.F.P. in maternal blood should become a screening test in all pregnancies, and a scheme for the futher investigation of patients with abnormal results is described.

CIRCULATING LEVELS OF PREGNANCY‐SPECIFIC β1‐GLYCOPROTEIN IN EARLY PREGNANCY

Circulating levels of pregnancy‐specific β1‐glycoprotein (SP1 or PSβG), luteinizing hormone (LH) and human chorionic gonadotrophin (HCG) were measured serially in 9 subjects immediately after conception. Ovulation occurred spontaneously in 3 subjects, or followed administration of clomiphene citrate (2 subjects) or bromocriptine (4 subjects). The timing of ovulation was determined by the appearance of the LH surge. Levels of HCG were detected 10 to 16 days, and SP1, 18 to 23 days after ovulation. These findings suggest that the measurement of plasma levels of SP1 may provide valuable additional biochemical evidence of pregnancy.

CIRCULATING LEVELS OF PREGNANCY-SPECIFIC β1−GLYCOPROTEIN AND HUMAN PLACENTAL LACTOGEN IN THE THIRD TRIMESTER OF PREGNANCY: THEIR RELATIONSHIP TO PARITY, BIRTH WEIGHT, AND PLACENTAL WEIGHT

Circulating levels of pregnancy‐specific β1‐glycoprotein (SP1) and human placental lactogen (HPL) were measured in 153 normal subjects during the third trimester of pregnancy. The levels of SP1 and HPL showed a skewed distribution and rose progressively to reach a plateau by the 36th week. The normal range was calculated by ranking the data and division into centiles as well as by logarithmic transformation of the values. A low but significant correlation was observed between SP1 and HPL levels, SP1 and birth weight. There was also a correlation between HPL levels and placental weight.

ALPHA-FETOPROTEIN LEVELS IN PREGNANCIES COMPLICATEED BY GASTROINTESTINAL ABNORMALITIES OF THE FETUS

Alpha‐fetoprotein (AFP) levels have been measured in maternal serum and amniotic fluid in a variety of gastrointestinal abnormalities of the fetus. Maternal serum AFP levels were consistently elevated in abdominal wall defects of the fetus after 15 weeks gestation and the amniotic fluid levels were raised in 3 of the 4 patients measured. In atresia of the gastrointestinal tract and diaphragmatic hernia, serum AFP levels were usually normal unless there was an associated neural tube defect or multiple pregnancy, although the majority were not measured between 15 and 26 weeks gestation. If elevated amniotic fluid levels of AFP are used in the decision to terminate pregnancy on the assumption of a probable neural tube defect of the fetus, a proportion of terminations will be performed because of abdominal wall defects of the fetus.

The Development of Radioimmunoassays for Fibrinogen Degradation Products: Fragments D and E

Summary. Fibrinogen degradation products, fragment D (FgD) and fragment E (FgE) have been measured in human serum by specific radioimmunoassays. In addition, the appearance of a neoantigenic determinant on FgD, revealed when fibrinogen is degraded by plasmin has been utilized to develop a specific radioimmunoassay for FgD in plasma (FgDneo). The reagents and conditions used in each assay are described in detail. The mean specific activity was 144 μCi/μg for 125I‐labelled FgE and 82 μCi/μg for 125I‐labelled FgD. Separation of antibody bound and free antigen was achieved using second antibody. The detection limits of the FgE, FgD and FgDneo assays were 0.8, 1.0 and 6.2 ng/ml respectively. The specificity of each assay with respect to fibrinogen and its degradation fragments has been assessed. Fibrinogen and fragment X cross‐reacted markedly in both the FgE and FgD assays, whereas the cross‐reaction of fibrinogen was abolished in the FgDneo assay, while the cross‐reaction of fragment X was 10%, indicating gradual emergence of the neoantigenic site during digestion of fibrinogen. The sensitivity, precision, and specificity of the radioimmunoassay systems described have major advantages over the existing procedures for the measurement of fibrinogen degradation products.

PLASMA FERRITIN LEVELS AS AN INDEX OF IRON DEFICIENCY IN WOMEN USING INTRAUTERINE DEVICES

Forty‐seven women were studied before and for one year after insertion of an intrauterine contraceptive device (IUCD). The menstrual blood loss increased in 44 subjects (94 per cent), and this was related to the surface area of the IUCD. Plasma ferritin levels in the iron deficient range (below 16 ug/l) were present in 9 subjects (19 per cent) before insertion of the IUCD, whereas by the end of one year, 21 subjects (45 per cent) had reached these levels. The incidence of depressed ferritin levels was highest in subjects with a monthly blood loss exceeding 80 ml. The haemoglobin, mean corpuscular haemoglobin and mean corpuscular volume measurements declined progressively, but were less sensitive predictors of iron deficiency. These findings indicate the need to monitor iron status and administer oral iron replacement therapy in subjects with an IUCD.

SPECIFIC AND SENSITIVE DETERMINATION OF FIBRINOGEN-DEGRADATION PRODUCTS BY RADIOIMMUNOASSAY

Abstract Radioimmunoassays have been developed for the determination of serum levels of fibrinogen degradation products, fragment E (FgE) and fragment D (FgD), in man. In addition, FgD has been measured in plasma by a specific radioimmunoassay directed to a neoantigenic site on FgD revealed when fibrinogen is degraded by plasmin (FgD neo ). The detection limits of the FgE, FgD, and FgD neo assays were 0·2, 2, and 5 ng. per ml., respectively. In eighteen healthy volunteers the serum levels ranged from 73 to 603 ng. per ml. for FgE, from 328 to 2744 ng. per ml. for FgD, and from 73 to 298 ng. per ml. for FgD neo ; the plasma levels of FgD neo were 44-211 ng. per ml. Raised levels were found in ten patients after major surgical procedures. It is suggested that the sensitivity and specificity of this type of assay have major advantages over the existing procedures for the measurement of fibrinogen degradation products.